Water-soluble Derivative Research Articles

Development and validation of an LC‒MS/MS method for the determination of cyclocreatine phosphate and its related endogenous biomolecules in rat heart tissues

The cardioprotective drug cyclocreatine phosphate has been awarded Food and Drug Administration-orphan drug designation for the prevention of ischemic injury to enhance cardiac graft recovery and survival in heart transplantation. Cyclocreatine phosphate is the water-soluble derivative of cyclocreatine. Estimating the levels of Cyclocreatine phosphate, Adenosine triphosphate, Creatine Phosphate, Creatine and Cyclocreatine helps us in understanding the energy state as well as evaluating the heart cells’ function. The quantification of endogenous compounds imposes a challenging task for analysts because of the absence of a true blank matrix, whose use is required according to international guidelines. Recently, the International Council for Harmonization issued a new guideline that contains guidance on the validation of methods used to quantify endogenous components, such as the background subtraction approach that was employed in our current study. Specifically, we developed and validated a sensitive, reliable and accurate liquid chromatography-tandem mass spectrometry assay to determine simultaneously the levels of mentioned endogenous compounds in rat heart tissue. Tissue samples were prepared by protein precipitation extraction using water: methanol (1:1). Using Ultra Performance Liquid Chromatography, Chromatographic separation was achieved with ZORBAX Eclipse Plus C18 4.6 × 100 mm,3.5 μm column and conditions as following: ammonium acetate (pH 8.5): acetonitrile, 70:30 mobile phase, 0.7 mL/min flow rate and 25 °C temperature. Electrospray ionization mass detector with Multiple reaction monitoring mode was then employed, using both positive and negative modes, Analysis was carried out using 5.00–2000.00 ng/mL linear concentration range within 2 min for each analyte. According to Food and Drug Administration guidelines for bioanalytical methods, validation was carried out. We investigated the matrix effect, recovery efficiency and process efficiency for the analyte in neat solvent, postextraction matrix and tissue. The results stated mean percentage recoveries higher than 99%, accuracy 93.32–111.99%, and Relative Standard Deviation (RSD) below 15% within the concentration range of our study which indicated that target analytes’ stability in their real matrix is sufficient under the employed experimental conditions.

Water-Soluble Curcumin Derivatives Including Aza-Crown Ether Macrocycles as Enhancers of their Cytotoxic Activity.

The synthesis of three novel curcumin derivative compounds, featuring aza-crown ether macrocycles of various sizes (aza-12-crown-4, aza-15-crown-5, and aza-18-crown-6), is described. The incorporation of these aza-crown macrocycles significantly enhances their water solubility, positioning them as groundbreaking instances of curcumin derivatives that are fully soluble in aqueous environments. These curcumin ligands (L1, L2, and L3) were then reacted with zinc acetate to afford the coordination metal complexes (L1-Zn, L2-Zn, and L3-Zn). Comprehensive characterization of all compounds was achieved using various analytical techniques, including 1D and 2D NMR spectroscopy, ATR-FTIR spectroscopy, mass spectrometry (ESI+), elemental analysis and UV-Vis spectroscopy. The in vitro cytotoxic activity of both, ligands and complexes were evaluated on three human cancer cell lines (U-251, MCF-7, and SK-LU-1). Compared to conventional curcumin, these compounds demonstrated improved antiproliferative potential. Additionally, a wound healing assay was conducted to assess their antimigration properties. The obtained results suggest that these modifications to the curcumin structure represent a promising approach for developing therapeutic agents with enhanced cytotoxic properties.

Novel phthalocyanines bearing fluoro-methylquinolin substituents: Synthesis, characterization, photophysical and photochemical properties

The novel 4-((6-fluoro-2-methylquinolin-4-yl)oxy)phthalonitrile (3a), 3-((6-fluoro-2-methylquinolin-4-yl)oxy)phthalonitrile (3b), tetra 6-fluoro-2-methylquinolin-4-yl)oxy substituted zinc(II) phthalocyanines (4a and 4b) and their water soluble derivatives (5a and 5b) were prepared. The proposed structures of novel compounds were comfirmed via FT-IR, 1HNMR , UV–Vis and MALDI-TOF mass data. The aggregation tendency, fluorescence quantum yield, singlet oxygen quantum yield and photodegradation measurements were performed to examine the photodynamic therapy potential of both peripherally tetra substituted zinc(II) phthalocyanines (4a and 4b) and the water soluble quaternized tetra substituted zinc(II) phthalocyanines (5a and 5b). The result showed that both the novel tetra 6-fluoro-2-methylquinolin-4-yl)oxy substituted zinc(II) phthalocyanines (4a and 4b) and their water soluble derivatives (5a and 5b) could be used as photosensitizer agents in PDT thanks to their lack of aggregation tendency, having sufficient fluorescence emission for monitoring and produce high amount of singlet oxygen to destroy cancerous tissues and having moderate photostability.

Dose-Response Effect of Various Concentrations of Cl-Containing Water-Soluble Derivatives of C60 Fullerenes on a Selective Regulation of Gene Expression in Human Embryonic Lung Fibroblasts (HELF).

The new synthesized water-soluble derivatives of C60 fullerenes are of a great interest to researchers since they can potentially be promising materials for drug delivery, bioimaging, biosonding, and tissue engineering. Surface functionalization of fullerene derivatives changes their chemical and physical characteristics, increasing their solubility and suitability for different biological systems applications, however, any changes in functionalized fullerenes can modulate their cytotoxicity and antioxidant properties. The toxic or protective effect of fullerene derivatives on cells is realized through the activation or inhibition of genes and proteins of key signaling pathways in cells responsible for regulation of cellular reactive oxygen species (ROS) level, proliferation, and apoptosis. The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay was used to assess cells viability. Flow cytometry analyses was applied to measure proteins levels in human embryonic lung fibroblasts (HELF) cells. HELF is a standard, stable and well described human cell line that can be passaged many times. Quantitation of ROS was assessed using H2DCFH-DA. Fluorescence images were obtained using microscopy. Expression of BCL2, CCND1, CDKN2A, BRCA1, BAX, NFKB1, NOX4, NRF2, TBP (reference gene) was analyzed using real-time Polymerase chain reaction (PCR). We found that high and low concentrations of fullerene C60 derivatives with the five residues of potassium salt of 6-(3-phenylpropanamido)hexanoic (F1) or 6-(2-(thiophen-2-yl)acetamido)hexanoic (F2) acid and a chlorine atom attached directly to the cage cause diametrically opposite activation of genes and proteins of key signaling pathways regulating the level of oxidative stress and apoptosis in HELF. High concentrations of F1 and F2 have a genotoxic effect, causing NADPH oxidase 4 (NOX4) expression activation in 24-72 hours (2-4 fold increase), ROS synthesis induction (increase by 30-40%), DNA damage and breaks (2-2.5 fold 8-oxodG level increases), and activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) (by 40-80%) against the background of reduced NF-E2-related factor 2 (NRF2) expression (by 20-45%). Low concentrations of F1 and F2 produced a cytoprotective effect: in 24-72 hours they reduce the oxidative DNA damage (by 20-40%), decrease the number of double-strand DNA breaks (by 20-30%), increase the level of anti-apoptotic proteins and enhance the antioxidant response activating the NRF2 expression (NRF2 gene expression increases 1.5-2.3 fold, phosphorylated form of the NRF2 protein increases 2-3 fold). Obtained results show that in low doses studied fullrens may serve as perspective DNA protectors against the damaging genotoxic factors.

Synthesis of Multivalent Glycoside-Immobilized Carboxymethyl Cellulose Nanohydrogel Particles with Superadsorption Ability for Lectins.

Carboxymethyl cellulose (CMC) is a water-soluble cellulose derivative that is nontoxic, biocompatible, biodegradable, and nonallergenic. As developing an adsorbent material for carbohydrate-binding proteins is challenging, we aimed to synthesize CMC nanohydrogel particles (CMCGPs) with an extremely high lectin adsorption tendency in this study. CMCGPs were used as the backbone of an adsorption carrier that was synthesized by cross-linking CMC with ethylene glycol diglycidyl ether. A series of glycoside-immobilized CMCGPs were synthesized by binding two types of glycans (LacNAc and lactose) to the polyvalent carboxymethyl groups that are present on the CMCGP surface and act as reaction sites. These immobilized glycosides function as molecular recognition sites. Glycan moieties were incorporated into the CMCGP backbone at degrees of immobilization (DI) ranging from 8.7 to 21.0% by altering the reaction composition. LacNAc-CMCGP (3b) showed a 19.9% DI of LacNAc glycoside to the CMCGP carboxymethyl group; on average, its particle size swelled to 418 nm in phosphate-buffered saline, which is approximately 1.4 times its dry-state size. Analyzing the adsorbent properties of glyco-CMCGPs using a lectin-binding assay showed the high structural specificity of glyco-CMCGPs to lectins. The equilibrium isotherm data was explained by the Langmuir adsorption model. Notably, compound 3b adsorbed 1.95 ± 0.05 μg of wheat germ agglutinin (WGA) lectin per 1.0 μg-dry of 3b particles at an adsorption equilibrium time of a few minutes. Furthermore, solid-state 13C nuclear magnetic resonance analysis showed that WGA lectin retained its natural structure without denaturation after binding to LacNAc-CMCGP. These results were also supported by affinity purification experiments of WGA from raw wheat germ extract using LacNAc-CMCGP, demonstrating that glyco-CMCGP is capable of adsorbing and desorbing lectin while maintaining its biological activity. Thus, multivalent glycoside-immobilized CMCGPs that use woody biomass derivatives as the backbone are expected to be applied as biorefinery materials, which specifically and abundantly adsorb not just plant lectins but also pathogenic viruses and toxin proteins.

Chitosan-curcumin conjugate prepared by one-step free radical grafting: Characterization, and functional evaluation

Curcumin (Cur) is a naturally hydrophobic polyphenol, and it has a wide range of physiological functions. But the practical application of Cur is constrained by its low water solubility and poor stability. To improve these deficiencies of Cur, a novel Cur derivative (CS-Cur) was prepared by grafting chitosan (CS) with Cur through a one-step reaction of a free radical-mediated redox system. A series of characterizations provided evidence that the grafting of CS with Cur was successful. The obtained CS-Cur showed lower crystallinity and thermal properties than CS and Cur. After grafting, the water solubility of CS-Cur was found to be 9.76±2.45 g/L and greatly improved. Meanwhile, the CS-Cur showed good photothermal stability, antioxidant activity, and photodynamic antibacterial activity in an aqueous solution, and it had good in vitro biosafety. This provides an idea for the design and synthesis of novel highly water-soluble Cur derivatives and also improves the practical application of Cur in aqueous systems.

Therapeutic Responses to Two New SN-38 Derivatives in Colorectal Cancer Patient-Derived Xenografts and Respective 3D In Vitro Cultures.

SN-38, an active metabolite of irinotecan, exhibits toxicity to all proliferating cells, causing dose-limiting and potentially life-threatening side effects. Newly established water-soluble derivatives of SN-38, 7-ethyl-9-(N-morpholinyl)methyl-10-hydroxycamptothecin (BN-MOA) and 7-ethyl-9-(N-methylamino)methyl-10-hydroxycamptothecin (BN-NMe), exhibit a unique mechanism of spontaneous alkylation of aromatic bases in DNA and show greater in vitro activity on cancer cell lines than SN-38. The aim of this study was to compare the therapeutic responses to irinotecan, BN-MOA and BN-NMe in vivo and in vitro in 3D cultures using colorectal cancer (CRC) patient derived xenografts (PDX). Seven established PDX tissues were subcutaneously grown on the flanks of NSG or NSG-SGM3 mice and tumor diameters were measured with a caliper. Compounds were administrated intraperitoneally at 40 mg/kg every five days. 3D PDX cultures were performed on 96-well LifeGel plates and cell viability was determined with the CellTiter Glo 3D reagent. Treatment with irinotecan significantly delayed or stopped the growth of 5 out of 7 PDXs, with a greater level of inhibition from BN-MOA compared to irinotecan and BN-NMe. In vitro studies exhibited the same trends in SN-38 and BN-NMe but not in BN-MOA. The new SN-38 derivatives, BN-MOA and BN-NMe, showed enhanced therapeutic effects compared to irinotecan in CRC models. BN-MOA demonstrated superior tumor inhibition in vivo, while BN-NMe had similar in vitro activity to SN-38. These findings highlight the potential of BN-MOA for greater antitumor efficacy in vivo, with BN-NMe showing comparable effectiveness to SN-38 in vitro. Future studies should optimize growth models to better predict anticancer drug responses.

Design, synthesis, and activity evaluation of water-soluble propofol derivatives as anesthetic drugs

In this work, two series of water-soluble derivatives were designed and synthesized based on the structure of propofol as the lead compound. Furthermore, the anesthetic activities of the synthesized compounds were evaluated in vivo against mice, and the in vitro propofol release rate from five target compounds was determined. The findings of this study have shown that series II compounds which possess the structure feature of propofol + γ-hydroxybutyric acid + α-aminoacetate or γ-aminobutyrate have higher therapeutic index than that of series I compounds which possess the structure feature of propofol + α-aminoacetate or β-aminopropionate. In addition, the rate of propofol released from series II compounds was significantly better than that of series I compounds. Among series II compounds, compound II-20 had a therapeutic index of 5.6 (propofol = 2.7), a duration time of 571 s (propofol = 57 s), and no significant toxicity was observed in vivo, which made it valuable for further development.

WazaGaY: An Innovative Aza-BODIPY-Derived Near-Infrared Fluorescent Probe for Enhanced Tumor Imaging.

Aza-BODIPYs represent a class of fluorophores in which the π-conjugated system is rigidified and stabilized by a boron atom. A promising strategy to enhance their fluorescence properties involves replacing the boron atom with a metal ion. Here, we describe the synthesis and characterization of a water-soluble derivative where the metal is a gallium(III) ion, termed WazaGaY (water-soluble aza-GaDIPY). Water solubility is ensured by two ammonium substituents, inducing a bathochromic shift and a significant increase in quantum yield compared to that of the dimethylamino analog. The cellular behavior of WazaGaY-1 was observed across different tumor cells. In vivo, the distribution and safety profiles were determined, and tumor uptake was assessed in various tumor types. Following intravenous injection, WazaGaY-1 enabled clear discrimination of tumors engrafted subcutaneously in mice with high tumor-to-muscle ratios (ranging from 7 to 20), even in the absence of specific conjugation. Its potential as a contrast agent for fluorescence-guided surgery was confirmed.

Modulating the spirolactone−zwitterion equilibrium of dichlororhodamine via changing its aqueous solubility: A new strategy to construct glutathione fluorogenic probe for bioimaging

The aqueous solubility is one of the key physical properties of a fluorophore. Herein, we synthesized and evaluated a series of 4,5-dichlororhodamine 19 (DCR) derivatives and demonstrated that the spirolactone-zwitterion equilibrium of DCR scaffold is highly dependent on its aqueous solubility: poor water-soluble DCR derivatives predominately adopt as a colorless, non-fluorescent spirolactone in neutral aqueous solution, whereas good water-soluble ones favor a colored, fluorescent zwitterion. To confirm the validity of this strategy, a hydrophobic benzyl thioester functionality was introduced to DCR platform to develop DCR-BTE as a fluorescent probe for glutathione (GSH). The transthioesterification between DCR-BTE and the thiol group of GSH affords a new thioester containing a good water-soluble GSH residue (DCR-GSH), thus shifting the equilibrium toward the fluorescent open form. DCR-BTE was proved to be capable of reporting the variations of GSH levels within the physiological concentration range, and its potential biological utility was shown by monitoring the depletion of GSH in the liver and kidney tissues of mice administrated by an overdose of acetaminophen. The present study provides an appealing strategy to construct fluorogenic probes based on tuning the lactone-zwitterion equilibrium of rhodamine via changing its aqueous solubility.

Amino polycarboxylic acids-modified abiraterone derivatives as potential injectable anti-prostate cancer agents

Abiraterone (Abi), an effective cytochrome oxidase P450 C17 (CYP17) inhibitor, inhibits androgen synthesis in testes, adrenal glands, and prostate tumors. However, their low bioavailability and dissolution rate due to their poor solubility and toxic side effects have hindered their clinical applications. In this study, water-soluble and injectable Abi derivatives were developed by introducing amino polycarboxylic acids into Abi, and their antiproliferation effects in vitro, mechanism of action, antitumor activities in vivo, pharmacokinetics, and toxicity were investigated. Compared to Abi, the water-soluble derivative Abi-DTPA exhibited excellent antitumor activity in vitro and in vivo. It decreased cell migration, invasion, and mitochondrial membrane potential. A mechanistic study revealed that it still targeted the CYP17 enzyme and increased the expression levels of apoptosis-related proteins, including cleaved caspase 9, cleaved PARP, and cleaved caspase 3. Abi-DTPA was the main form in the plasma and exhibited lower toxicity after intravenous administration. These findings suggest that Abi-DTPA can be used as a novel injectable anti-prostate cancer agent.

Insight into the therapeutic effects of artesunate in relieving metabolic-associated steatohepatitis from transcriptomic and lipidomics analyses.

Artesunate (ART) is a water-soluble derivative of artemisinin, which has shown anti-inflammatory, anti-tumor, and immunomodulating effects. We aimed to investigate the potential therapeutic effects and mechanisms of ART in metabolic dysfunction-associated steatohepatitis (MASH). The mice were randomly divided into the control group, high-fat, high-cholesterol diet-induced MASH group, and the MASH treated with ART (30 mg/kg once daily) group. Liver enzymes, lipids, and histological features were compared among groups. The molecular mechanisms were studied by transcriptomic and lipidomics analyses of liver tissues. The mice of the MASH group had significantly increased hepatic fat deposition and inflammation in terms of biochemical indicators and pathological manifestations than the control group. The ART-treated group had improved plasma liver enzymes and hepatic cholesterol, especially at week 4 of intervention (p < 0.05). A total of 513 differentially expressed genesand 59 differentially expressed lipids were identified in the MASH group and the MASH+ART group. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment test showed that ART regulated glycerolipid metabolism pathway and enhanced fatty acid degradation. Peroxisome proliferator-activated receptor (PPAR)-α acted as a key transcription factor in the treatment of MASH with ART, which was confirmed by cell experiment. ART significantly improved fat deposition and inflammatory manifestations in MASH mice, with potential therapeutic effects. The mechanism of artemisinin treatment for MASH may involve extensive regulation of downstream genes by upstream transcription factors, such as PPAR-α, to restore hepatic lipid homeostasis.

New Antibacterial and Antioxidant Chitin Derivatives: Ultrasonic Preparation and Biological Effects.

This work focuses on the first use of ultrasonic phenol-ene coupling as a polymer analogous transformation. The ultrasonic reaction was introduced into chitin chemistry, resulting in the fast and convenient preparation of new water-soluble cationic chitin derivatives. Since water-soluble derivatives of fully deacetylated chitin are poorly described in the literature, the synthesis of each new type of these derivatives is a significant event in polysaccharide chemistry. Polycations, or cationic polymers, are of particular interest as antibacterial agents. Consequently, the resulting polymers were tested for their antibacterial activity and toxicity. We found that the highly substituted polymer of medium molecular weight exhibited the most pronounced in vitro antibacterial effect. We prepared nanoparticles using the ionic gelation technique. The most effective in vitro antibacterial chitin-based systems were tested in vivo in rats. These tests demonstrated outstanding antibacterial effects combined with an absence of toxicity. Additionally, we found that the resulting polymers, unlike their nanoparticle counterparts, also exhibited strong antioxidant effects. In summary, we demonstrated the effectiveness of ultrasound in polymer chemistry and highlighted the importance of the sonochemical approach in the chemical modification of polysaccharides. This approach enables the synthesis of derivatives with improved physicochemical and biological properties.

New gel from a water-soluble Carboxymethyl chitosan-Cinnamaldehyde Schiff base derivative as an effective preservative against soft rot in ginger

Ginger, valued for its culinary and medicinal properties, suffers substantial production loss—up to 90 %—due to fungal soft rot. To combat this, we have developed an environmentally sustainable antifungal polysaccharide gel derived from a water-soluble Schiff base of O-carboxymethyl chitosan (CMC) and cinnamaldehyde (CIN). Terpene incorporation was confirmed via various characterization techniques, including Fourier transform infrared (FT-IR), pH-dependent release, solubility, thermogravimetric analysis, and UV–vis spectra. Results showed successful grafting of CIN onto the polysaccharide, at a CIN:CMC ratio of 120 mg/g. In vitro evaluation demonstrated significant antifungal activity against F. oxysporum, with a MIC value of 159.25 μg/mL. Application of the CMC=CIN gel to ginger rhizomes inhibited spore germination in all evaluated wounds, enhancing gloss and appearance. These findings validate the efficacy of this novel, environmentally friendly gel in preventing ginger loss caused by fungal infections.

Physical, antibacterial, blood coagulation, and healing promotion evaluations of chitosan derivative-based composite films

Chitosan is a potentially suitable material for wound dressing, but is undesirably water-insoluble. Although chitosan can be modified to produce water-soluble derivatives, the best chitosan derivative for wound dressings remains unclear. The present study introduced three water-soluble chitosan derivatives, namely, carboxymethyl chitosan, quaternized chitosan (QCS), and carboxymethyl quaternized chitosan, and explored the physical properties, biochemical properties, and wound care effectiveness of films of these derivatives. The QCS-based film exhibited higher absorption ability, mechanical properties, water-vapor permeability, electroconductivity, and antioxidant capacity than the other films. Most importantly, the cationic quaternary ammonium groups facilitated the antibacterial activity (>95 %) and blood coagulant capacity of the QCS-based film. As this film also promoted wound healing, it presented as an ideal candidate for wound dressings.

Multiscale Computational Study of Cellulose Acetate-Water Miscibility: Insights from Molecularly Informed Field-Theoretic Modeling.

Cellulose acetate (CA), a prominent water-soluble derivative of cellulose, is a promising biodegradable ingredient that has applications in films, membranes, fibers, drug delivery, and more. In this work, we present a molecularly informed field-theoretic model for CA to explore its phase behavior in aqueous solutions. By integrating atomistic details into large-scale field-theoretic simulations via the relative entropy coarse-graining framework, our approach enables efficient calculations of CA's miscibility window as a function of the degree of substitution (DS) of cellulose hydroxyl groups with acetate side chains. This allows us to capture the intricate phase behavior of CA, particularly its unique miscibility at intermediate substitution, without relying on experimental input. Additionally, the model directly probes CA solution behavior specific to the relative DS at C2, C3, and C6 alcohol sites, providing insights for the rational design of water-soluble CA for diverse applications. This work demonstrates a promising integration of molecularly informed field theories, complementing wet-lab experimentation, for engineering the next-generation polymeric materials with precisely tailored properties.

Synthesis and comparison of the performance of two different water-soluble phthalocyanine based electrochemical biosensor

Herein, a comparative study between novel water-soluble phthalocyanine-based biosensors was performed for the application of glucose sensing. For this purpose, two different copper (II) and manganese (III) phthalocyanines and their water-soluble derivatives were synthesized, and then their role as a supporting material for enzyme immobilization was evaluated by comparing their sensor performances. Two different phthalocyanine (AP-OH2-MnQ (MnPc) and AP-OH2-CuQ (CuPc)) were tested using electrochemical biosensor with immobilized glucose oxidase (GOx). To the best of our knowledge, the related water-soluble phthalocyanine-based glucose biosensors were attempted for the first time, and the developed approach resulted in improved biosensor characteristics. The constructed biosensors GE/MnPc/GOx and GE/CuPc/GOx showed good linearity between 0.003–1.0 mM and 0.05–0.4 mM, respectively. The limit of detection was estimated at 0.0026 mM for the GE/MnPc/GOx and 0.019 mM for the GE/CuPc/GOx. KMapp and sensitivity values were also calculated as 0.026 mM and 175.043 µAmM−1 cm−2 for the GE/MnPc/GOx biosensor and 0.178 mM and 117.478 µAmM−1 cm−2 for the GE/CuPc/GOx biosensor. Moreover, the fabricated biosensors were successfully tested to detect glucose levels in beverages with high recovery results. The present study shows that the proposed water-soluble phthalocyanines could be a good alternative for quick and cheap glucose sensing with improved analytical characteristics.

Optimization of Interfacial Properties Improved the Stability and Activity of the Catalase Enzyme Immobilized on Plastic Nanobeads.

The immobilization of catalase (CAT), a crucial oxidoreductase enzyme involved in quenching reactive oxygen species, on colloids and nanoparticles presents a promising strategy to improve dispersion and storage stability while maintaining its activity. Here, the immobilization of CAT onto polymeric nanoparticles (positively (AL) or negatively (SL) charged) was implemented directly (AL) or via surface functionalization (SL) with water-soluble chitosan derivatives (glycol chitosan (GC) and methyl glycol chitosan (MGC)). The interfacial properties were optimized to obtain highly stable AL-CAT, SL-GC-CAT, and SL-MGC-CAT dispersions, and confocal microscopy confirmed the presence of CAT in the composites. Assessment of hydrogen peroxide decomposition ability revealed that applying chitosan derivatives in the immobilization process not only enhanced colloidal stability but also augmented the activity and reusability of CAT. In particular, the use of MGC has led to significant advances, indicating its potential for industrial and biomedical applications. Overall, the findings highlight the advantages of using chitosan derivatives in CAT immobilization processes to maintain the stability and activity of the enzyme as well as provide important data for the development of processable enzyme-based nanoparticle systems to combat reactive oxygen species.

Synthesis and cholinesterases inhibitory effects of water soluble zinc(II) and silicon(IV) phthalocyanines bearing ({8‐[3‐(dimethylamino)phenoxy]octyl}oxy) groups

Alzheimer's disease, is one of the irreversible neurodegenerative disorders among older people, causes behavior, memory, and thinking problems. This study aim is to synthesize of 4‐({8‐[3‐(dimethylamino)phenoxy]octyl}oxy)phthalonitrile, zinc(II) phthalocyanine and its water soluble derivative containing ({8‐[3‐(dimethylamino)phenoxy]octyl}oxy) substituents at the peripheral positions first time. To determine the potential of water soluble silicon(IV) and zinc(II) phthalocyanines for use in AD, spectrophotometric assays were performed to determine their acetylcholinesterase/butyrylcholinesterase inhibitory effects. In addition, their DNA nuclease properties were evaluated by agarose gel electrophoresis. The results showed that the compounds inhibited acetylcholinesterase/butyrylcholinesterase. They did not damage pBR322 plasmid DNA depending on time and concentration. As a result of the experiments, it is revealed that the compounds may be the potential for use as cholinesterase inhibitors, which is a promising approach for the treatment of Alzheimer's disease.

Anti-tumor and anti-metastasis of water-soluble sulfated β-glucan derivatives from Saccharomyces cerevisiae

Traditional fungi β-glucan commonly possesses high molecular weight with poor water solubility, which remains significant challenge in the drug development and medical application. Water-soluble β-glucan with high molecular weight (dHSCG) of 560 kDa, low molecular weight (dLSCG) of 60 kDa, and sulfated derivative (SCGS) with a molecular weight of 146 kDa and sulfate degree at 2.04 were obtained through well-controlled degradation and sulfated modification from Saccharomyces cerevisiae in this study. The structural characteristics were confirmed as β-1,3/6-glucan by FT-IR and NMR spectroscopy. Carbohydrate microarrays and surface plasmon resonance revealed distinct and contrasting binding affinities between the natural β-glucans and sulfated derivatives. SCGS exhibited strong binding to FGF and VEGF, while natural β-glucan showed no response, suggesting its potential as a novel antitumor agent. Moreover, SCGS significantly inhibited the migration rate of the highly metastatic melanoma (B16F10) cells. The lung metastasis mouse model also demonstrated that SCGS significantly reduced and eliminated the nodules, achieving an inhibition rate of 86.7% in vivo, with a dramatic improvement in IFN-α, TNF-α, and IL-1β levels. Through analysis of protein content and distribution in lung tissues, the anti-tumor and anti-metastasis mechanism of SCGS involves the regulation of degrading enzymes to protect extracellular matrix (ECM), as well as the reduction of angiogenic factor release. These findings provide a foundation for exploring the potential of SCGS in the development of new anti-tumor and anti-metastasis drugs and open up a new field in cancer research.